Effects of prenatal opioid exposure on functional networks in infancy.
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ABSTRACT:
SUBMITTER: Merhar SL
PROVIDER: S-EPMC8363826 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life.
| S-EPMC4224027 | biostudies-literature
Project description:ImportancePrenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions.ObjectiveTo compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE.Design, setting, and participantsThis retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462).ExposurePrenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD]).Main outcomes and measuresThe main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023.ResultsNeonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE.Conclusions and relevanceIn this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.
| S-EPMC10794935 | biostudies-literature
Project description:AimThis systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies.MethodsWe searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using "Covidence" systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment.ResultsData were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis.ConclusionWe explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.
| S-EPMC9989202 | biostudies-literature
Project description: Not available
| S-EPMC7890532 | biostudies-literature
Project description:The influence of proinflammatory challenges, such as maternal immune activation (MIA) or postnatal exposure to drugs of abuse, on brain molecular pathways has been reported. On the other hand, the simultaneous effects of MIA and drugs of abuse have been less studied and sometimes offered inconsistent results. The effects of morphine exposure on a pig model of viral-elicited MIA were characterized in the prefrontal cortex of males and females using RNA-sequencing and gene network analysis. Interacting and main effects of morphine, MIA, and sex were detected in approximately 2000 genes (false discovery rate-adjusted p-value < 0.05). Among the enriched molecular categories (false discovery rate-adjusted p-value < 0.05 and -1.5 > normalized enrichment score > 1.5) were the cell adhesion molecule pathways associated with inflammation and neuronal development and the long-term depression pathway associated with synaptic strength. Gene networks that integrate gene connectivity and expression profiles displayed the impact of morphine-by-MIA interaction effects on the pathways. The cell adhesion molecules and long-term depression networks presented an antagonistic effect between morphine and MIA. The differential expression between the double-challenged group and the baseline saline-treated Controls was less extreme than the individual challenges. The previous findings advance the knowledge about the effects of prenatal MIA and postnatal morphine exposure on the prefrontal cortex pathways.
| S-EPMC9407090 | biostudies-literature
Project description:Prenatal exposure to addictive drugs can lead to placental epigenetic modifications, but a methylome-wide evaluation of placental DNA methylation changes after prenatal opioid exposure has not yet been performed. Placental tissue samples were collected at delivery from 19 opioid-exposed and 20 unexposed control full-term pregnancies. Placental DNA methylomes were profiled using the Illumina Infinium HumanMethylationEPIC BeadChip. Differentially methylated CpG sites associated with opioid exposure were identified with a linear model using the ‘limma’ R package. To identify differentially methylated regions (DMRs) spanning multiple CpG sites, the ‘DMRcate’ R package was used. The functions of genes mapped by differentially methylated CpG sites and DMRs were further annotated using Enrichr. Differentially methylated CpGs (n = 684, unadjusted p < 0.005 and |∆β| ≥ 0.05) were mapped to 258 genes (including PLD1, MGAM, and ALCS2). Differentially methylated regions (n = 199) were located in 174 genes (including KCNMA1). Enrichment analysis of the top differentially methylated CpG sites and regions indicated disrupted epigenetic regulation of genes involved in synaptic structure, chemical synaptic transmission, and nervous system development. Our findings imply that placental epigenetic changes due to prenatal opioid exposure could result in placental dysfunction, leading to abnormal fetal brain development and the symptoms of opioid withdrawal in neonates.
| S-EPMC9138340 | biostudies-literature
Project description:BackgroundPrenatal opioid exposure has been linked to adverse birth outcomes and delays in infant development. Existing literature is limited by a simple group-differences approach as well as inadequate controls for sociodemographic factors and polysubstance exposure co-occurring with prenatal opioid use.MethodThe current study assessed cumulative opioid exposure (duration of prescribed and illicit opioid use) as a predictor of infant birth outcomes and mother-reported developmental status at three and six months of age, controlling for polysubstance exposure. Participants were predominantly low-income pregnant and peripartum women, oversampled for mothers receiving medication-assisted treatment (MAT) for opioid use disorder. Prenatal opioid and non-opioid substance use were reported by mothers using a Timeline Follow-Back Interview completed during the third trimester and updated postnatally (infant age six months).ResultsDevelopmental scores were in the normal range. However, total opioid exposure was positively related to premature birth and inversely related to mother-reported developmental status in specific domains. Associations with three-month fine motor skills and six-month communication skills were robust to controls for polysubstance exposure and sociodemographic covariates.ConclusionsResults suggest unique effects of prenatal opioid exposure on the early development of fine motor and communication skills. Similar findings were obtained for prescribed and illicit opioid use, underscoring developmental risks of both MAT and untreated substance use. Exploratory analyses investigating type and timing of MAT suggest directions for future research.
| S-EPMC8277730 | biostudies-literature
Project description:Background/objectivePer- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood.MethodsWe included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR).ResultsAmong six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (β = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03).ConclusionsPrenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.
| S-EPMC8119322 | biostudies-literature
Project description:As the opioid crisis has continued to grow, so has the number of infants exposed to opioids during the prenatal period. A growing concern is that prenatal exposure to opioids may induce persistent neurological changes that increase the propensity for future addictions. Although alcohol represents the most likely addictive substance that the growing population of prenatal opioid exposed will encounter as they mature, no studies to date have examined the effect of prenatal opioid exposure on future sensitivity to alcohol reward. Using a recently developed mouse model of prenatal methadone exposure (PME), we investigated the rewarding properties of alcohol and alcohol consumption in male and female adolescent PME and prenatal saline exposed (PSE) control animals. Conditioned place preference to alcohol was disrupted in PME offspring in a sex-dependent manner with PME males exhibiting resistance to the rewarding properties of alcohol. Repeated injections of alcohol revealed enhanced sensitivity to the locomotor-stimulating effects of alcohol specific to PME females. PME males consumed significantly more alcohol over 4 weeks of alcohol access relative to PSE males and exhibited increased resistance to quinine-adulterated alcohol. Further, a novel machine learning model was developed to employ measured differences in alcohol consumption and drinking microstructure to reliably predict prenatal exposure. These findings indicate that PME alters the sensitivity to alcohol reward in adolescent mice in a sex-specific manner and suggests prenatal opioid exposure may induce persistent effects on reward neurocircuitry that can reprogram offspring behavioural response to alcohol later in life.
| S-EPMC8896285 | biostudies-literature
Project description:BackgroundThe impact of prenatal opioid exposure on brain development remains poorly understood.MethodsWe conducted a prospective study of term-born infants with and without prenatal opioid exposure. Structural brain MRI was performed between 40 and 48 weeks postmenstrual age. T2-weighted images were processed using the Developing Human Connectome Project structural pipeline. We compared 63 relative regional brain volumes between groups.ResultsTwenty-nine infants with prenatal opioid exposure and 42 unexposed controls were included. The groups had similar demographics, except exposed infants had lower birth weights, more maternal smoking and maternal Hepatitis C, fewer mothers with a college degree, and were more likely non-Hispanic White. After controlling for sex, postmenstrual age at scan, birth weight, and maternal education, exposed infants had significantly smaller relative volumes of the deep gray matter, bilateral thalamic ventrolateral nuclei, bilateral insular white matter, bilateral subthalamic nuclei, brainstem, and cerebrospinal fluid. Exposed infants had larger relative volumes of the right cingulate gyrus white matter and left occipital lobe white matter.ConclusionsInfants with prenatal opioid exposure had smaller brain volumes in multiple regions compared to controls, with two regions larger in the opioid-exposed group. Further research should focus on the relative contributions of maternal opioids and other exposures.ImpactPrenatal opioid exposure is associated with developmental and behavioral consequences, but the direct effects of opioids on the developing human brain are poorly understood. Prior small studies using MRI have shown smaller regional brain volumes in opioid-exposed infants and children. After controlling for covariates, infants with prenatal opioid exposure scanned at 40-48 weeks postmenstrual age had smaller brain volumes in multiple regions compared to controls, with two regions larger in the opioid-exposed group. This adds to the literature showing potential impact of prenatal opioid exposure on the developing brain.
| S-EPMC8110593 | biostudies-literature